Ion-specificity and surface water dynamics in protein solutions

Abstract

Ion-specific effects at the protein surface are investigated here in light of the changes they infer to surface water dynamics, as observed by 1H NMR relaxation (at 20 MHz). Two well-known proteins, hen egg-white lysozyme (LZM) and bovine serum albumin (BSA), show qualitatively opposite trends in the transverse relaxation rate, R2(1H), along a series of different monovalent salt anions in the solution. Presence of salt ions increases R2(1H) in the case of lysozyme and diminishes it in the case of BSA. The effect magnifies for larger and more polarizable ions. The same contrasting effect between the two proteins is observed for protein-solvent proton exchange. This hints at subtle effects ion-binding might have on the accessibility of water surface sites on the protein. We suggest that the combination of the density of surface charge residues and surface roughness, at the atomic scale, dictates the response to the presence of salt ions and is proper to each protein. Further, a dramatic increase in R2(1H) is found to correlate closely with the formation of protein aggregates. The same ordering of salts in their ability to aggregate lysozyme, as seen previously by cloud point measurements, is reproduced here by R2(1H). 1H NMR relaxation data is supplemented by 35Cl and 14N NMR relaxation for selected salt ions to probe the ion-binding itself.

Phase stability of aqueous mixtures of bovine serum albumin with low molecular mass salts in presence of polyethylene glycol

“…As a direct consequence of the water asymmetry, the anions have a stronger hydration than the cations: (i) since the oxygen atom of water is quite electronegative, it is easier for water to accept a negative charge from the anions than to accept a positive charge from the cations, and (ii) anions interacting with the hydrogen atoms of water can facilitate inter-shell hydrogen bonding between water molecules [ 2 , 60 ]. A number of experimental studies have confirmed that the influence of anions on protein solutions is much greater than the influence of cations [ 56 , 55 ] (even at p H ≫ p I [ 57 ]). When some of the salt anions bind to the protein surface of a net neutral protein molecule ( p H = p I), the effect is the same as when the protein is in a solution with p H slightly above p I ( p H > p I).…”

“…In several of our previous works, we have shown that thermodynamic properties, such as enthalpy changes upon dilution or mixing in polyelectrolyte solutions [ 59 , 62 , 63 , 57 ], or alternatively, cloud-point temperature data for protein solutions [ 28 ] correlate well with hydration properties of low molecular mass salt ions. The correlation of the T c with the Gibbs free energy of hydration, Δ hyd G , of the low molecular mass salt ions used in this work is examined in Fig.…”

Multiscale Water Dynamics on Protein Surfaces: Protein-Specific Response to Surface Ions

“…The data in Figure 1 are clearly consistent with our previous measurements at a single frequency of 20 MHz, which showed an increased sensitivity of R 2 (transverse NMR relaxation rate), as opposed to R 1 , to the salt specific effects in LZM and BSA solutions. 37 Importantly, the current multi-frequency data incite the development and allow the testing of a multi-scale model of the water dynamics at protein surfaces, in order to explain the protein-specific response in Figure 1. The model considers both long-lived ("embedded") and short-lived ("transiently diffusing") water molecules on the protein surface.…”

NMR Relaxation of Nuclei of Buffer as a Probe for Monitoring Protein Solutions Including Aggregation Processes

“…Torres et al have shown the applicability of this model for RNA, (1) 1∕T 1 = P free ∕T 1,free + P bound ∕ T 1,bound + bound , BSA, and sodium dodecyl sulfate (SDS) micelles that justify it as universal for biomolecules [27]. Similar studies were performed using 14 N, 35 Cl, and 37 Cl nuclei [28][29][30][31][32].…”